The present invention relates to the field of prosthetic urethral valves or seals for controlling urinary continence. More particularly, the present invention relates to a prosthetic urethral device having an opening pressure that varies in response to changes in physiologic parameters. The present invention also introduces unique cohesive bioadhesive materials which may be used to form prosthetic urethral valves having the aforementioned properties, as well as other biomedical devices.
Urinary incontinence is a widespread problem in the United States and throughout the world. Urinary incontinence affects people of all ages and can severally impact a patient both physiologically and psychologically. Urinary incontinence has a number of causes, including birth defects, disease, injury, aging, and urinary tract infection.
In light of the foregoing, a number of attempts have been made to combat urinary incontinence. One such attempt involves the use of a catheter connected to a collection bag with a clamping device on the catheter. Indwelling catheters, however, have a number of drawbacks. For instance, there is an infection risk associated with indwelling catheters, which provide a direct passage for bacteria or other microorganisms into the bladder. Thus, indwelling catheters can only be used for relatively short-term situations. In addition, indwelling catheters and associated collection bags are not cosmetically appealing to most patients.
The prior art prosthetic urethral valves also have numerous disadvantages. For instance, many prior art urethral valves utilize an inflatable cuff around the outside of the urethra. One disadvantage of such a valve is that it requires surgery for installation. In addition, such a valve must be operated externally and thus is dependent on manual intervention. Moreover, the prosthetic urethral valves of the prior art tend to be generally rigid and noncompliant in structure and some tend to dilate the urethra over time. This may result in deterioration of the natural anatomy, which leaves the patient in worse physical condition.
Intraurethral valves of the prior art also generally require manual intervention. Another problem associated with prior art intraurethral valves is that they may be displaced or migrate into the bladder or expelled from the urethra. There is also an infection risk associated with many such valves since they extend into the meatus and/or have portions of the device external to the urethra providing a passage for micro-organisms into the bladder.
Thus, there remains a need for a nonsurgically installed prosthetic urethral valve or seal that responds to physiological conditions and thus can be controlled voluntarily by the patient without manual intervention. Furthermore, there is a need for prosthetic urethral valves having structure or being composed of materials which inhibit valve migration from the urethra into the bladder.
Advantageously, the present invention provides an intrauretheral valve for controlling urinary incontinence which overcomes many of the shortcomings of the prior art. Valves of the present invention may be introduced nonsurgically, and are formed of novel cohesive bioadhesive materials which nonpermanently bond the valve to the inner lumen of the urethra. Consequently, valves of the present invention are less likely to migrate into the bladder. Furthermore, the bioadhesive compositions used to make the valves may also be used to form all or part of a variety of other biomedical devices.
In one aspect of the present invention, there is provided an intraurethral device for maintaining urinary continence comprising an elongate body having a proximal end, a distal end, and a flow path extending therebetween. The body has an outer surface formed of a bioadhesive material comprising a copolymer resulting from the polymerization of one or more types of carboxyl functional monomers and one or more types of hydrophobic monomers. In some embodiments, the carboxyl functional monomers may be selected from the group consisting of acrylic acid, methacrylic acid, ethyl acrylic acid, propyl acrylic acid, butyl acrylic acid and combinations of the foregoing. The hydrophobic monomers may have a phenyl ring moiety, and in certain embodiments, be selected from the group consisting of phenyl ethyl methacrylic acid, phenyl ethyl acrylic acid, phenyl methyl methacrylic acid, phenyl methyl acrylic acid, benzyl acrylic acid, benzyl methacrylic acid and combinations of the foregoing. Alternatively, the hydrophobic monomer may comprise one or more (meth-)acrylimide monomers.
In one preferred embodiment, the volume ratio of carboxyl functional monomers to hydrophobic monomers in the reaction used to make the copolymer is initially between about 20:1 and 1:2, more preferably between about 10:1 and 1:1, and optimally between about 10:2 and 10:4.
The intraurethral device may also have an inner surface defining the central lumen, the inner surface being formed of a soft polymeric material having a Young""s modulus between 1 KPa and 10 MPa, and preferably having a Young""s modulus of between 10-100 KPa. In one aspect of this embodiment, there is a middle layer between the outer surface and the inner surface. The middle layer may be formed of an elastomeric material or material having elastomeric properties. Thus, the middle layer may be optionally formed from a material selected from the group consisting of silicone, polyurethane and polyacrylate elastomers.
In another aspect of the present invention, there is provided an intraurethral device for maintaining urinary continence, comprising a three-layered elongate body with a proximal end, a distal end, and a flow path extending therebetween. The three-layered body has an outer layer comprising a bioadhesive material, a middle layer comprising an elastomeric material, and an inner layer comprising a soft polymeric material.
In another aspect of the present invention, there is provided a method of adhering a medical device to a tissue surface. The method comprises providing a medical device having a bioadhesive surface. The bioadhesive surface is formed as a copolymer from the polymerization of at least a first monomer having a carboxyl functional moiety and at least a second monomer having a hydrophobic moiety. The bioadhesive surface is adhered to the tissue by contacting the bioadhesive surface to the tissue surface.
In another aspect of the present invention, there is provided a method of forming a medical device with a bioadhesive surface. The method comprises copolymerizing at least a first carboxyl functional moiety-bearing monomer with at least a first hydrophobic moiety-bearing monomer to form a bioadhesive copolymer. The copolymer has a tensile strength of at least about 10 psi. The bioadhesive copolymer is provided as a surface combined with a medical device, such the surface remains exposed for adhesion to a tissue.
In another aspect of the present invention, there is provided a bioadherent substrate. The substrate has a surface portion comprising a bioadhesive copolymer which selectively adheres to tissues. The copolymer has a tensile strength of at least 10 psi and transmits at least 80% of the visible light passing through it per millimeter of thickness of the copolymer.
In another aspect of the present invention, there is provided a bioadherent medical device. The bioadhesive medical device has a bioadhesive surface comprising a copolymer having at least one carboxyl functional monomeric unit resulting from copolymerization of a monomer selected from the group consisting of 
X=xe2x80x94H, xe2x80x94CH3, xe2x80x94CH2CH3 
and at least one hydrophobic monomeric unit resulting from copolymerization of a hydrophobic monomer selected from the group consisting of 
Z=xe2x80x94H, xe2x80x94CH3, or xe2x80x94CH2CH3 
Y=nothing or O
Ar=C1-C3 alkyl substituted aromatic ring or unsubstituted aromatic ring
n=1-5
or
R1=C1-C5 alkyl substituted aromatic ring or unsubstituted aromatic ring
R2=hydrogen or C1-C5 alkyl group.
In another aspect of the present invention, there is provided a method of manufacturing a medical device for removable attachment to a tissue surface. The first step of the method is to provide a medical device having at least one tissue contacting surface. A coating is applied to the tissue contacting surface. The coating comprises a polymerization product of at least a first monomer having a carboxyl functional moiety and at least a second monomer having a hydrophobic monomer moiety.
In another aspect of the present invention, there is provided a method of manufacturing a medical device by applying a cohesive bioadhesive to the entire exposed surface of the medical device. Optionally, the medical device and the coating may be impregnated with a drug.
In another aspect of the present invention, there is provided a method of releasably adhering a medical device to a tissue surface. The medical device has a surface thereon comprising an adhesive composition. A site in or on a patient for implantation of the device is then identified. The surface of the medical device is then contacted with tissue at the site to adhere the device to tissue. Preferably, the adhesive surface has a tensile strength in excess of about 10 psi and comprises a homogeneous copolymer capable of providing adhesion to a tissue surface in an aqueous environment. The site may be a body lumen, as for example the esophagus, intestine, urethra, ureter, veins and arteries. The site may be a subcutaneous tissue surface, or the site may be a hollow organ.
Medical devices incorporating the cohesive bioadhesives described above may be used in a variety of clinical applications. For example, the devices may function as facilitating devices, flow regulating devices, monitoring devices, and other types of medical devices requiring adhesion to tissue.
In one application, the medical device is a plug for reducing the available volume of a vascular anomaly, such as for treatment of vascular aneurysm or arteriovenous fistula.
In a different application, medical devices incorporating bioadhesives of the present invention may be applied to the surface of an organ, as for example, for treatment of an ulceration in the surface of the organ.
Optionally, medical devices incorporating the bioadhesives of the present invention may be used to release a medication from the medical device into the site. In these and other applications, the medical device may be adhered to the site for a period of time within the range of from about 1 to about 30 days. In some circumstances, the medical device might be absorbed at the site.
In another application of the present invention, there is provided a drug delivery device for the time release of a drug into adjacent tissue. The device comprises the polymerization product of at least a first monomer have a carboxyl functional moiety and at least a second monomer having a hydrophobic moiety, and at least one drug.
In another application of the present invention, there is provided a wound closure patch, such as for closing a subcutaneous aperture or surgical incision, comprising the polymerization product of at least a first monomer having a carboxyl functional moiety and at least a second monomer having a hydrophobic moiety. The patch may be in the form of a flexible sheet.
In another application of the present invention, there is provided a vascular plug for obstructing blood flow through a vessel, comprising a radially outwardly facing annular surface having thereon a polymerization product of at least a first monomer having a carboxyl functional moiety and at least a second monomer having a hydrophobic moiety.